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Neuroscience > SAKMANN AND NEHER INVENT PATCH-CLAMPING > Flashcards

SAKMANN AND NEHER INVENT PATCH-CLAMPING Flashcards

1
Q

A method to measure the behavior of a single ion channel

A

SAKMANN AND NEHER

PATCH-CLAMPING

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2
Q

Erwin Neher and Bert Sakmann invented a new technique called patch
clamping, which allowed them to study the

A

behavior of a single ion channel

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3
Q

1991 Nobel Prize in Medicine or Physiology

A

Neher and

Sakmann

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4
Q

The ion channel is

inserted in the

A

membrane that is

in the lumen of the electrode,

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5
Q

However, whether
open for a longer or shorter period, the conductance of the Na channel (the amount of current passed
during any instant in time) is always the same. T/F

A

True

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6
Q

individual channel opens and closes

A

very rapidly

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7
Q

channels have ___ conductances

A

unitary

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8
Q

If the same depolarizing pulse was presented a
second time, or a third or fourth time, the same inward current pattern was evoked. This pattern
of current flowing through the entire axon is called the

A

macroscopic current

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9
Q

patterns of inward current evoked in a single Na channel, called the

A

microscopic current,

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10
Q

The opening and closing of an individual channel was variable because the behavior of any
channel is

A

probabilistic.

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11
Q

What the membrane potential does is to change the ___that a

channel will open.

A

probability

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12
Q

In the case of the Na channel, depolarization increases the probability that the

A

activation gate will open.

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13
Q

hyperpolarization

increases the probability of

A

closing the Na activation gate

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14
Q

depolarization increases the probability that the inactivation gate will

A

close

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15
Q

hyperpolarization

increases the probability that the inactivation gate will

A

open

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16
Q

How then do we reconcile the stereotyped current response of the squid giant axon to a
depolarization of -10 mV, the shape of the macroscopic current, with the highly variable
response of an individual Na channel, the microscopic current, to exactly the same
depolarization?

A

squid giant
axon during voltage clamp shows the summated (or averaged) currents through many ion
channels in the entire membrane of the axon rather than the current through a single channel.

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17
Q

was simple to calculate

the probability of a Na channel opening as a function of

A

membrane potential

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18
Q 
function of membrane potential. That function is
shown in Fig. 4E, and has a \_\_\_shape
A

sigmoidal

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19
Q

inward currents are

shown as

A

downward deflections

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20
Q

Current through a single

channel is called the

A

microscopic

current

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21
Q 
The sum of many such
microscopic currents shows that most
channels open in the initial\_\_\_after
which the probability of channel
openings diminishes because of channel
inactivation.
A

1-2 ms,

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22
Q

The macroscopic
current resulting from the current
flowing through all of the Na channels
while

A

voltage clamping the entire axon

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23
Q

is very similar

to the summed microscopic current in C.

A

macroscopic current

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24
Q

The probability of Na channel

opening depends on the

A

membrane

potential,

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25
Q

Notice that the
probability is virtually zero (few or no
channels open) at

A

-60 to -80 mV

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26
Q

probability of channel opening is about
80% even when the membrane is
depolarized to

A

+40 mV

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27
Q

Depolarizing steps cause outward currents which are seen as

A

(upward

deflections

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28
Q

Notice that the K channel opens with different
latencies to the depolarization and that the channels
stay open for the length of the

A

depolarization,

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29
Q

the probability-membrane
potential function is similar to both the K
conductance-membrane potential function and to the
Na conductance-membrane potential function

T/F

A

T

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30
Q

Strong hyperpolarization virtually ensures that
52
activation gates are closed, since the probability of a Na or K channel being open at ____
is just about zero (

A

-70-80 mV

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31
Q

the open probability increases

sharply with depolarization at these values

A

-40 to 0 mV

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32
Q

max probability at

A

+30 mV.

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33
Q

What is somewhat surprising however is that the maximum open probability is not 100%
but rather only

A

70-80%

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34
Q

hyperpolarization

guarantees gate closure whereas depolarization only makes gate opening more likely. T/F

A

T

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35
Q

he probability that the channel can pass Na+ ions decreases after the
depolarization

A

been present for a period of time due to the closure of the inactivation gate

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36
Q

The delayed closure can be appreciated from the records in Fig. 2 and Fig. 4B, since there were
no channel openings after the first

A

first 8.0 msec or so of the depolarizing pulse.

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37
Q

It has been known that if a nerve axon is hyperpolarized for a period of time, an
action potential is often set off when the hyperpolarization is released and the cell quickly
brought back to rest; this is called

A

anode break excitation or rebound excitation.

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38
Q

explanation for rebound excitation is that

A

hyperpolarization of the membrane increases

the number of Na channels available for opening in response to depolarization

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39
Q

why the states of the activation and

inactivation gates are “probabilistic”.

A

This “flickering” between states

even when the membrane potential is not changing,

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40
Q

The larger number of Na channels open when the membrane potential was brought back to
rest allowed a correspondingly

A

larger influx of Na+ ions

41
Q

two features of axons that determine velocity

A

axon diameter; and 2) myelination

42
Q

larger the axon diameter, the ___ the conduction velocity

A

faster

43
Q

The longer the advance of the current, the ____ the action potential propagates

A

faster

44
Q

How far the local
current spreads down the axon depends upon two features that act as resistances to current flow. They
are;

A

membrane resistance, and 2) the internal resistance of the axon

45
Q

The membrane resistance is determined simply by the

A

number of open ion channels in the
membrane.

(K+ channels that set the resting potential, that
is, the K+ channels that are NOT gated by voltage but are always open.)

46
Q

refers to how difficult it is for current to flow down the axon.

A

internal resistance

47
Q

The internal resistance refers to how difficult it is for current to flow down the axon. Obviously,
the larger the diameter, the ___resistance there is to flow.

A

less

48
Q

larger axons have a ____ internal resistance, and hence it is easier for current to flow down the axon and depolarize long segments
of the axon

A

lower

49
Q

the larger the axonal diameter, the ___the membrane resistance and the
more current that leaks out along the axon

A

smaller

50
Q

membrane resistance acts to oppose the

effects of

A

internal resistance

51
Q

Thus decreasing membrane resistance ___the time it takes for the axon to reach threshold

A

lengthens

slow conduction velocity

52
Q

The question is, which of the two features dominates, internal resistance or
membrane resistance?

A

internal resistance

53
Q

Membrane resistance is

determined by the

A

axonal

circumference

54
Q

internal

resistance is determined by

A

area of

the axon.

55
Q

changes as the square of the radius
and thus changes faster with
diameter

A

Internal resistance

56
Q

Circumference of circle

A

2 x pi x r

57
Q

area of a circle

A

pi x r^2

58
Q

are those that are voltage insensitive, i.e., are not influenced by voltage

A

Passive

properties

59
Q

Passive

properties are

A

conduction velocity, membrane resistance, internal

resistance and capacitance

60
Q

active properties that are voltage sensitive,

such as

A

voltage gated Na+ and K+ channels

61
Q

electrical component that simply is an insulator that separates and thereby stores charges

A

capacitor

62
Q

The quantitative feature of a capacitor is called its

A

capacity.

63
Q

simply the amount of charge

required to change the potential across the capacitor by 1 millivolt.

A

capacity.

64
Q

Capacity =

A

Capacity =

Q/ V, where Q is charge (coulombs) and V is voltage.

65
Q

So the passive properties are determined by three principal features:

A

1) membrane resistance; 2)

membrane capacitance and 3) internal resistance.

66
Q

each

patch is connected to the next patch of membrane through the

A

internal resistance (ri).

67
Q

other words, the charge across capacitor in patch 1 experiences the

A 
greatest
change (the largest depolarization).
68
Q

Each successive patch of membrane

receives less current than the previous patch because; 1

A

1) much of the current has already been used to
depolarize the set of capacitors closest to the current source; and 2) some of the current has leaked out in
the initial patches through open channels that form the membrane resistance.

69
Q

If the depolarization of the membrane potential at patch 1 is sufficiently large, the signal is
prevented from dying out by

A

active processes that are voltage dependent

70
Q

nature has done in vertebrates is to add

A

myelin sheaths to smaller axons

71
Q

Since all membranes

are made of lipids, the fatty wrapping, called myelin, forms an

A

insulation, just

72
Q

The insulation prevents current from leaking out along the length of the insulated portion, i.e., it
massively increases

A

membrane resistance

73
Q

The entire length of the axon is not insulated without

interruption. Rather, there are bare spots located periodically along the axon called

A

nodes of Ranvier.

74
Q

All voltage gated Na+ and K+ channels are densely packed at the

A

nodes of Ranvier.

75
Q

What

happens, in essence, is that the action potential in a myelinated axon

A

skips from node to node

76
Q

This type of conduction used by myelinated axons is called

A

saltatory conduction

77
Q

saltatory conduction

Latin saltare,

A

hop or leap

78
Q

The largest myelinated axons in our nervous system have diameters of only

A

20 micrometers (recall that the diameter of the squid giant axon is 800-1000 micrometers

79
Q

an
unmyelinated fiber would have to be___ in diameter to conduct as fast as the most rapid myelinated
fibers.

A

4 mm

80
Q 
Multiple sclerosis (abbreviated MS) is an inflammatory disease in which the fatty myelin sheaths
around the axons of the brain and spinal cord are
A

damaged or degenerate

81
Q

The name multiple

sclerosis refers to scars (scleroses—better known as plaques or lesions) particularly in the

A

white matter

of the brain and spinal cord, which is mainly composed of myelin

82
Q

In MS, the body’s own immune

system attacks

A

oligodendrocytes,

83
Q

there are non-voltage gated K+ channels but no voltage-gated

Na+ or K+ channels under the

A

myelin sheaths (

84
Q

conduction

velocity in vertebrates is determined by both

A

myelination and axon diameter.

85
Q

Our unmyelinated axons have conduction velocities of around

A

1 meter/sec,

86
Q

myelinated nerve fibers conduct from

A

10-120 meters/sec

87
Q

The recording electrodes are on the surface of the nerve and record the
summated action potentials of all the fibers as they travel along the nerve. This recording is

A

compound action potential

88
Q

compound action potential has three major components

A

first
component evoked reflects the arrival of the fastest (largest) myelinated axons and is called the A
component.

smaller myelinated axons and is called the B
component.

slowest axons are unmyelinated

89
Q

touch, joint position,

muscle stretch and sharp pain

A

A component

90
Q

slow pain and temperature

receptors,

A

C component.

slowest axons are unmyelinated

91
Q

The fastest fibers are called

A

Aa fibers

92
Q

next fastest are

A

Ab fibers

93
Q

slowest A fibers are

the

A

Ag fibers

94
Q

The nerves of the

peripheral nervous system are

A

mixed nerves;

95
Q

action potentials in the

axons of motor neurons move

A

orthodromically) toward their muscles in the thumb

96
Q

action potentials in the axons of the sensory fibers move

backward

A

antidromically

97
Q

the conduction velocity of both sensory and motor myelinated fibers is
slowed down, or even abolished, due to demyelination, whereas the conduction velocity of
unmyelinated fibers is normal

A

MS

98
Q

selective degeneration of motor neurons; sensory neurons
are not affected. The selective pathology and death of motorneurons is detectable by observing
decreased, slowed, or jittery motor components (at the base of the thumb) with normal sensory
components (at the fingertips since no motoneurons are present in the fingertips).

A

ALS also called Lou Gehrig’s

disease)

Neuroscience (6 decks)

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